FDA ALERT [6/16/2008]: FDA is notifying healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis.

In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics.

Antipsychotics are not indicated for the treatment of dementia-related psychosis.

This information reflects FDA’s current analysis of data available to FDA concerning these drugs. FDA intends to update this sheet when additional information or analyses become available.

To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program using the contact information at the bottom of this sheet.

FDA is requiring the manufacturers of conventional antipsychotic drugs to add a Boxed Warning and Warning to the drugs’ prescribing information about the risk of mortality in elderly patients treated for dementia-related psychosis similar to the Boxed Warning and Warning added to the prescribing information of the atypical antipsychotic drugs in 2005.* See the last page of this document for a list of conventional and atypical antipsychotic drugs.

Considerations for Healthcare Professionals

Elderly patients with dementia-related psychosis treated with conventional or atypical antipsychotic drugs are at an increased risk of death.

Antipsychotic drugs are not approved for the treatment of dementia-related psychosis. Furthermore, there is no approved drug for the treatment of dementia-related psychosis. Healthcare professionals should consider other management options.

Physicians who prescribe antipsychotics to elderly patients with dementia-related psychosis should discuss this risk of increased mortality with their patients, patients’ families, and caregivers.

Background Information and Data

Previously, in April 2005, FDA informed healthcare professionals and the public about the increased risk of mortality in elderly patients receiving atypical antipsychotic drugs to treat dementia-related psychosis (April 2005 Public Health Advisory and Information for Healthcare Professionals). At that time, the analyses of 17 placebo-controlled trials that enrolled 5377 elderly patients with dementia-related behavioral disorders revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g. pneumonia) in nature. Based on this analysis, FDA requested that the manufacturers of atypical antipsychotic drugs include information about this risk in a Boxed Warning and the Warnings section of the drugs’ prescribing information.

Recently, two observational epidemiological studies1,2 were published that examined the risk of death in patients who were treated with conventional antipsychotic drugs.

Gill et al.1 performed a retrospective cohort study in Ontario, Canada of 27,259 adults, 66 years of age or older, with a diagnosis of dementia between April 1997 and March 2002. The investigators compared the risk for death with use of an atypical antipsychotic versus no antipsychotic and the risk for death with use of a conventional antipsychotic versus an atypical antipsychotic. They found that atypical antipsychotics were associated with increased mortality as compared to no antipsychotic use as early as 30 days and persisting until study end at 180 days. The investigators found that conventional antipsychotic use showed a marginally higher risk of death compared with atypical antipsychotic use. The causes of death were not reported in this study.

Schneeweiss et al.2 performed a retrospective cohort study in British Columbia, Canada of 37,241 adults, 65 years of age or older, who were prescribed conventional (12,882) or atypical (24,359) antipsychotic medications for any reason between January 1996 and December 2004. The investigators compared the 180-day all cause mortality with use of a conventional antipsychotic versus an atypical antipsychotic. They found that the risk of death in the group of patients treated with conventional antipsychotic medications was comparable to, or possibly greater than, the risk of death in the group of patients treated with atypical antipsychotic medications. The causes of death with the highest relative risk were cancer and cardiac disease.

FDA considers that the methodological limitations in these two studies preclude any conclusion that conventional antipsychotics have a greater risk of death with use than atypical antipsychotics. FDA has determined, however, that the overall weight of evidence, including these studies, indicates that the conventional antipsychotics share the increased risk of death in elderly patients with dementia-related psychosis that has been observed for the atypical antipsychotics. The prescribing information for all antipsychotic drugs will now include the same information about this risk in a Boxed Warning and the Warnings section.

*FDA is requiring the manufacturers to make these changes to the prescribing information for these drugs under its new authority to require safety label changes provided in Title IX of the FDA Amendments Act of 2007 (creating new section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act).

References

1. Gill SS et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146:775-786

2. Schneeweiss S et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ. 2007;176:627-632.

Conventional Antipsychotic Drugs Atypical Antipsychotic Drugs

Compazine (prochlorperazine) Abilify (aripiprazole)

Haldol (haloperidol) Clozaril (clozapine)

Loxitane (loxapine) FazaClo (clozapine)

Mellaril (thioridazine) Geodon (ziprasidone)

Moban (molindone) Invega (paliperidone)

Navane (thiothixene) Risperdal (risperidone)

Orap (pimozide) Seroquel (quetiapine)

Prolixin (fluphenazine) Zyprexa (olanzapine)

Stelazine (trifluoperazine) Symbyax (olanzapine and fluoxetine)

Thorazine (chlorpromazine)

Trilafon (perphenazine)

Source: http://www.fda.gov

Below are some common drug slang terms or drug street names:

STREET NAMES AND SLANG FOR HALLUCINOGENS
Marijuana
Pot, Reefer, Grass, Weed, Dope, Ganja, Mary Jane, or Sinsemilla, Urb,
Hashish
Hash
Mescaline and Peyote
Mesc, Buttons, and Cactus
Psilocybin (Shrooms)
Magic Mushrooms, ’shrooms
Lysergic acid diethylamide
Acid, Microdot, White lightning, Blue heaven, and Sugar Cubes
Analog of Amphetamines or Methamphetamines
MDMA (Ecstasy, XTC, Adam, Essence), MDM, STP, PMA, 2, 5-DMA, TMA, DOM, DOB, EVE
Phencyclidine
PCP, Hog, Angel Dust, Loveboat, Lovely
Analog of Phencyclidine (PCP)
PCPy, PCE

STREET NAMES AND SLANG FOR DEPRESSANTS
Nitrous Oxide
Laughing gas or Whippets
Amyl Nitrite
Poppers or Snappers
Butyl Nitrite
Rush, Bolt, Bullet, Locker Room, and Climax
Chloro-hydrocarbons
Aerosol sprays or cleaning fluids
Hydrocarbons
Solvents
Barbiturates
Downers, Barbs, Blue Devils, Red Devils, Yellow Jackets,
Yellows, Nembutal, Tuinals, Seconal, and Amytal
Methaqualone
Quaaludes, Ludes, Sopors
Tranquilizers
Valium, Librium, Serax, Equanil, Miltown, and Tranxene

STREET NAMES AND SLANG FOR STIMULANTS
Cocaine
Coke, Snow, Nose Candy, Flake, Blow, Big C, Lady, White, and Snowbirds, Powder,
Crack Cocaine
Crack, rock, freebase, Cookie,
Amphetamines
Speed, Uppers, Ups, Black beauties, Pep pills, Co-pilots, Bumblebees, Hearts, Benzedrine, Dexedrine, Footballs, and Biphetamine
Methamphetamines
Crank, Crystal meth, Crystal methadrine, and Speed
Additional Stimulants
Ritalin, Cylert, Preludin, Didrex, Pre-State, Voranil, Sandrex, and Plegine

STREET NAMES AND SLANG FOR NARCOTICS
Heroin
Smack, Horse, Mud, Brown sugar, Junk, Black tar, and Big H
Morphine
Pectoral syrup
Opium
Paregoric, Dover’s Powder, Parepectolin
Codeine
Empirin compound with codeine, Tylenol with codeine,
Codeine in cough medicine
Meperidine
Pethidine, Demerol, Mepergan
Analog of Fentanyl (Narcotic)
Synthetic heroin, China white
Analog of Meperidine (Narcotic)
MPTP (New heroin), MPPP, synthetic heroin

Source: http://www.njlawman.com/Feature%20Pieces/Drug%20Slang.htm

Two psychiatric medications made the list — Duloxetine (Cymbalta) for a serious risk of urinary retention, and Quetiapine (Seroquel) for overdose due to sample pack labeling confusion.

This is the FDA’s first new public information alert system in years, identifying potential safety issues in drugs and making that information available to the public. The list does not mean that FDA has identified a causal relationship between the drug and the listed risk, but that it’s investigating further to determine if such a relationship exists.

If you’re taking either of the two psychiatric drugs listed, or any of the other listed 18, you should talk to your doctor about the concern the FDA has identified. In terms of Cymbalta, you should talk to your doctor about any problems with retaining urine and in terms of Seroquel, you should double-check with your psychiatrist or doctor to ensure you’ve been prescribed the proper dose.

by John M. Grohol, Psy.D. September 5, 2008
Source: http://psychcentral.com/blog/archives/2008/09/05/two-psychiatric-drugs-on-fda-watch-list/

ZYPREXA is a brand name for a prescription medicine that is approved by the FDA for treating the symptoms of schizophrenia, acute mixed or manic episodes of bipolar I disorder and for maintenance treatment in bipolar disorder.

Important Safety Information

Facts About ZYPREXA
ZYPREXA has been prescribed to nearly 24 million people in 84 countries since its approval in 1996

ZYPREXA was the first of a newer generation of antipsychotic medications (called atypical antipsychotics) approved for the long-term treatment of schizophrenia

ZYPREXA was the first atypical antipsychotic approved for the treatment of acute bipolar mania

ZYPREXA has benefits in controlling positive symptoms (hallucinations, delusions) and negative symptoms (apathy, social withdrawal) of schizophrenia

ZYPREXA is easy to use — it can be taken once a day, with or without food

How ZYPREXA® (olanzapine) Works

ZYPREXA is a kind of medication known as an atypical antipsychotic. It belongs to a larger category of medications that affect the mind, called psychotropics. Antipsychotic medicines are psychotropic medications that treat the symptoms of psychotic disorders, such as schizophrenia. They may also be prescribed to treat acute mixed or manic episodes of bipolar disorder.
Antipsychotic Medicines

Antipsychotic medicines are believed to work by balancing the chemicals naturally found in the brain.

Antipsychotic medicines can be used to treat the symptoms of psychosis in schizophrenia, such as hallucinations and delusions, and may improve symptoms, such as fears and voices.

Antipsychotic medicines are also prescribed to treat acute mixed or manic episodes of bipolar disorder. They may improve such symptoms as sleep disturbances, irritability, racing thoughts, and anxiety. Some antipsychotic medications are also prescribed to help control ongoing symptoms.

When you start taking ZYPREXA, keep in mind that it can take several weeks before you notice a difference in the way you feel. The time it takes to experience the full effects of ZYPREXA may vary from person to person, depending on individual symptoms and the dosage prescribed.

It is important to take ZYPREXA the way your doctor has recommended — the right dose, at the same time, every day.

Managing Side Effects

Like any medicine, ZYPREXA may have some side effects. Medicines affect people in different ways. You may experience some of the side effects listed here.
The most common side effects of ZYPREXA are:
Drowsiness
Feeling more hungry than usual
Gaining weight
Dizziness
Dry mouth
Constipation
Upset stomach
Feeling weak
Restlessness
Tremors (shakes)

These side effects generally do not bother people enough to cause them to stop taking ZYPREXA. This is not a complete list of possible side effects. For a more complete list, read the important safety information. If you have questions, be sure to ask your doctor for more information. If you think you may be experiencing side effects, talk with your healthcare provider.

Dosing

Schizophrenia
Usual Dose — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.

Bipolar Disorder
Usual Monotherapy Dose — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.

Special Populations — The recommended starting dose is 5 mg in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (eg, nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be performed with caution in these patients.

Getting the Most From ZYPREXA® (olanzapine)

Unlike aspirin for a headache or medicine to relieve a cough, you probably can’t feel how ZYPREXA is helping relieve your symptoms. Keep in mind that it can take several weeks before you notice a difference in the way you feel. The time it takes to experience the full effects of ZYPREXA may vary from person to person, depending on individual symptoms and the dosage prescribed.
Create a Routine

It is important to take ZYPREXA the way your doctor has recommended — the right dose, at the same time, every day. Here are a few ways you can help yourself take ZYPREXA properly every day:
Take your medicine on a schedule that’s linked with certain activities you do every day (such as brushing your teeth, taking your vitamins, or eating breakfast or dinner. Or, set your medicine on the nightstand next to your bed or next to your favorite mug on the kitchen counter)

Organize your pills in a pill counter to keep track of the doses you’ve taken

Use a calendar to keep track of the doses you’ve taken

Ask your doctor if your medicine schedule can be changed so that you take fewer doses each day

Source: http://www.zyprexa.com/about_zyprexa.jsp

Antipsychotics can be classified by their structure but can also be distinguished by their pharmacology, their action at receptors, and by their clinical properties. Typical (also called conventional) antipsychotics act primarily at dopamine receptors. Atypical antipsychotics act on other receptors as well as dopamine, and are less likely than typical antipsychotics to cause movement disorders as a side effect. The following are atypical antipsychotics are licensed in the UK: amisulpiride (brand name Solian), aripiprazole (Abilify), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) and zotepine (Zoleptil).

As with all effective medicines antipsychotics can produce side effect in some individuals. The most common side effects include movement disorders that may resemble Parkinson’s disease (referred to as extrapyramidal effects, anticholinergic effects such as dry mouth, feelings of dizziness or light headedness, constipation and blurred vision (so called as they are due to the action of these drugs on cholinergic receptors in the brain and body) and weight gain.

It is important to appreciate that this is not a comprehensive list of the possible side effects of antipsychotics. Full guidance on prescribing and use, including possible side effects, of antipsychotics is provided in the Summary of Product Characteristics (SPC) for health professionals and the patient information leaflet (PIL) that should accompany the medicine.

More recently concerns have arisen that patients receiving risperidone and olanzapine in dementia were at an increased risk of stroke compared with patients receiving placebo (dummy pill) and that the balance of risks and benefits was considered to be unfavourable in the dementia population. Atypical antipsychotics are not authorised for the treatment of dementia related psychosis and/or behaviour disturbances. Prescribers were informed of this risk and advised to review the treatment of all patients receiving atypical antipsychotics in dementia as the risk of stroke for other atypical antipsychotics could not be excluded:
Source: http://www.mhra.gov.uk/Safetyinformation/Generalsafetyinformationandadvice/Product-specificinformationandadvice/Antipsychoticdrugs/index.htm